The overall goals of this project are to determine and compare the effects of morphine-like drugs and barbiturates on the cholinergic system in the brain. The present emphasis is on the effects of pentobarbital on transmitter release. Completed work has shown that pentobarbital can inhibit K-stimulated ACh release without necessarily causing an increase in tissue ACh levels. Recent studies have shown that this drug can inhibit the Ca#-dependent, K plus or minus stimulated release of other putative neurotransmitters (5HT, NE, GABA, glutamate, aspartate) from brain slices in vitro. Proposed studies for the following year include completion of a survey of the effects of several barbiturates and related drugs on ACh release in vitro and the evaluation of the development of tolerances to the inhibitory transmitter release in vitro after prolonged drug administration in vivo. BIBLIOGRAPHIC REFERENCES: Richter, Judith A. J. Neurochem. 26:791-797 (1976) Characteristics of Acetylcholine Release by Superfused Slices of Rat Brain. Richter, Judith A. Life Sciences 20:701-714 (1977) The Ionophone X537A (Lasolocid) Transiently Increases Acetylcholine Release from Rat Brain In Vitro.